【摘要】 目的:运用拟靶向代谢组学的方法对胶塞中的可提取物进行全面的分析。方法:以水、pH 2.6磷酸盐缓冲液、pH 9.18磷酸盐缓冲液、15%乙醇溶液分别对6种胶塞进行提取，制备质量控制(QC)溶液和供试品溶液。采用LC-30A超高效液相色谱仪-Q TOF-9030质谱ESI~+/ESI~-模式检测，使用Waters Acquity BEH C8/HSS T3色谱柱，以含0.1%甲酸的水-含0.1%甲酸的乙腈/含0.05%碳酸氢铵的水-含0.05%碳酸氢铵和5%水的甲醇作为流动相，运用TOF MS-和MS/MS DDA扫描模式对QC溶液进行检测。用MSConvert及MRM-Ion＿Pair＿Finder软件处理QC溶液的扫描结果，获得MRM参数。用ExionLC超高效液相色谱仪-Qtrap6500+质谱ESI~+/ESI~-模式检测，流动相和色谱柱同前，运用Scheduled-MRM扫描模式对提取液进行检测。结果:对1 399个未知物和116个已知物进行了分析，按提取液分类，发现pH 9.18磷酸盐缓冲液和15%乙醇溶液能提取出较多的化合物，找出了27个在不同提取液中差异较大的化合物；按胶塞分类，通过25个差异物，判断了不同胶塞的亲缘关系。结论:本研究对6种胶塞在4种提取物下的提取结果进行了分析。在不同的提取条件下，提取物之间存在差异。针对这些重点差异物可以专门制定分析方法进行质控跟踪研究，以确保药物质量的稳定和一致性。同时也分析了不同胶塞中的差异物，可以用来对未知胶塞样本进行大致的类别判断。更多还原

【Abstract】 Objective:To perform a comprehensive analysis of extractables in rubber by pseudotargeted metabolomics. Methods: The quality control(QC) solutions and test solutions were prepared by extracting the six kinds of rubbers with water, pH 2.6 phosphate buffer, pH 9.18 phosphate buffer, and 15% ethanol solution, respectively. The QC solutions were detected by LC-30A ultra performance liquid chromatography-Q TOF-9030 mass spectrometer in ESI~+/ESI~- mode. The mobile phases were 0.1% formic acid-water and 0.1% formic acid-acetonitrile/0.05% ammonium-water and 0.05% ammonium-5% water-methanol. The separation chromatographic column was Waters Acquity BEH C8/HSS T3. TOF MS and MS/MS DDA scanning modes were used to detect the QC solutions. The scan results of QC solution were processed with MSConvert and MRM-Ion＿Pair＿Finder software to obtain MRM parameters. The extracts were detected by ExionLC UPLC-Qtrap6500+ mass spectrometer in ESI~+/ESI~- mode with the same mobile phase and column as before, and Scheduled-MRM scan mode was applied to detect the extracts. Results: The 1 399 unknown compounds and 116 known compounds were analyzed. By extraction solution, it was found that pH 9.18 phosphate buffer and 15% ethanol solution could extract more compounds, and 27 compounds with large differences in different extraction solutions were identified. By rubbers, the affinities of different rubbers were determined by 25 differences. Conclusion: In this study, the results of the extraction of six rubbers under four extracts are analyzed. There are differences between extracts under different extraction conditions. Analytical methods can be specifically developed for these key variables for quality control follow-up studies to ensure the stability and consistency of drug quality. The variables in different rubbers are also analyzed, which can be used to make a general class determination of unknown rubber samples.更多还原